Parkinson Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, Barcelona, Spain.
Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
Ann Neurol. 2022 Nov;92(5):888-894. doi: 10.1002/ana.26469. Epub 2022 Sep 26.
The purpose of this study was to investigate whether differential phosphorylation states of blood markers can identify patients with LRRK2 Parkinson's disease (PD). We assessed phospho(P)-Ser-935-LRRK2 and P-Ser-473-AKT levels in peripheral blood cells from patients with G2019S LRRK2-associated PD (L2PD, n = 31), G2019S LRRK2 non-manifesting carriers (L2NMC, n = 26), idiopathic PD (iPD, n = 25), and controls (n = 40, total n = 122). We found no differences at P-Ser-935-LRRK2 between groups but detected a specific increase of P-Ser-473-AKT levels in all G2019S carriers, either L2PD or L2NMC, absent in iPD. Although insensitive to LRRK2 inhibition, our study identifies P-Ser-473-AKT as an endogenous candidate biomarker for peripheral inflammation in G2019S carriers using accessible blood cells. ANN NEUROL 2022;92:888-894.
本研究旨在探究血液标志物的磷酸化差异状态是否能识别 LRRK2 帕金森病（PD）患者。我们评估了 G2019S LRRK2 相关 PD（L2PD，n=31）、G2019S LRRK2 非表现型携带者（L2NMC，n=26）、特发性 PD（iPD，n=25）和对照组（n=40）患者外周血细胞中磷酸化（P）-Ser-935-LRRK2 和 P-Ser-473-AKT 水平。我们发现各组间 P-Ser-935-LRRK2 无差异，但在所有 G2019S 携带者（L2PD 或 L2NMC）中均检测到 P-Ser-473-AKT 水平特异性升高，而 iPD 中则无此升高。尽管对 LRRK2 抑制不敏感，但我们的研究使用可及的外周血细胞，确定 P-Ser-473-AKT 是 G2019S 携带者外周炎症的内源性候选生物标志物。ANN NEUROL 2022;92:888-894.
